Profiles of women in science: Malú Gámez Tansey, Norman and Susan Fixel Professor of Neuroscience and Neurology, Co-Director of the Center for Translational Research in Neurodegenerative Disease and Director of the Parkinson's Foundation Research Center of Excellence, University of Florida College of Medicine.

Abstract

We at EJN are pleased to introduce Dr. Malú Gámez Tansey as the next scientist for our series of Women in Neuroscience. We began this series to bring visibility and recognition to women scientists in our community (Helmreich et al., 2017); you can find all of the previous profiles online (https://onlinelibrary.wiley.com/doi/toc/10.1111/(ISSN)1460-9568.women-in-science). Dr. Tansey's lab explores the interactions between the nervous and immune systems in the context of health and disease. An example of her work can be found here: Immune system responses in Parkinson's disease: Early and dynamic (Tansey & Romero-Ramos, 2019). A brief description of Dr. Tansey's training and career: Malú Gámez Tansey, PhD, earned her BS/MS from Stanford University and her PhD from University of Texas Southwestern and did postdoctoral work at Washington University on GDNF/Ret signalling. She spent a year at Xencor, where she co-invented dominant-negative soluble TNF inhibitors currently in clinical trials for Alzheimer's disease and COVID-19. Today, she is the Norman and Susan Fixel Chair in Neuroscience and Neurology and Co-director of the Center for Translational Research in Neurodegenerative Disease at the University of Florida College of Medicine in Gainesville. Her lab focuses on the role of inflammation and immune system responses in brain health and mechanisms underlying development of neurodegenerative diseases (https://www.michaeljfox.org/researcher/malu-g-tansey-phd). I had the pleasure of speaking with Dr. Tansey in October 2021. EJN: How did you decide to become a neuroscientist? What started your journey? Dr. Tansey: I have always been interested in science. I think what got me interested in neuroscience initially was my interest in excitable cells; I trained as a cell physiologist in graduate school at UT Southwestern, working on smooth muscle contraction. I then got very interested in the brain and became a trained neuroscientist during my postdoc years at Wash U. There I studied: How is it that despite having good trophic support in the brain, there are certain neurons that are still vulnerable to death in neurodegenerative diseases? That was fascinating to me. At the end of my post-doc, I decided to go to the private sector; I wanted to work nine to five, make more money. I was there for a short time and learned a lot about immunology and inflammation, developing novel inhibitors of soluble TNF (tumor necrosis factor). I realized, though, that I was missing hypothesis-driven science, I was missing mentoring the students, and I wanted to come back to academia. I basically married my two interests and went back to academia asking the question: What is the role of inflammation in the brain, in terms of killing or damaging neurons in age-related neurodegenerative diseases? I was able to use our novel tools and inhibitors in my new lab with a material transfer agreement. Have you ever looked back? Not at all; I'm so involved in a rich network of good things—science and collaborations. I love training the next generation of students, they keep me on my toes and teach me a lot. I also think things are different now; the partnerships among pharma, biotech, and academia are much stronger (the federal government is part of that tripartite), and I think it is going to take all three sectors to solve these problems. I've also been very fortunate to be part of foundations and organizations that set-up pre-competitive spaces, like the Michael J. Fox Foundation, where scientists are free to share information and form collaborative teams. How do you build a good mentor–mentee relationship? Great question. I think it takes a lot of trust. It takes a lot of two-way, good communication between mentor and mentee; you have to be open and vulnerable. You have to be able to hear your own weaknesses, and your own areas in need of development from your own trainees. They're all scientific children, right? Each of them is different. So, what's really important for a mentor is to figure out which buttons to push in every one of them to help them become their best selves, and they are going to have different needs at different times during their scientific careers. And even after they leave the lab, you are still in touch with them, and hopefully you will have the capacity to continue to support them well into their own independent careers. They may compete with you and keep you on your toes then too. Do you have any advice for young women or anybody thinking of a career in neuroscience and research? Absolutely. I'll echo Maria Carrillo (Chief Science Officer of the Alzheimer's Association) and say to be brave and do difficult things. Do not settle for the easy stuff. Do not be intimidated by the competition. My postdoc mentor, Gene Johnson would always say first of all, have fun, but do not look over your shoulder at the competition as that just wastes precious time. Do the best experiment you can do, take care of the science, and the science will take care of you. I also think failure teaches you much more than success does. I would say that you could work on things that nobody else is working on, and nobody will ever compete with your work. But then you have to wonder, well, if nobody else is working on it, how important can it be? There's a certain amount of excitement in having others come to the table to work on things that you started working on and were once thought to be not too important. The role of glia and inflammation has changed 180 degrees since I was in school; you must have hit some resistance when you were starting up. When we started working on the role of inflammation in the brain in 2002, and when I set up my lab, nobody really thought there was anything there. I remember an associate professor at UT Southwestern stand up as soon as I started giving my very first seminar as a junior faculty, and he said, “What did you say? Inflammation in Parkinson's Disease? That's not a thing.” And I said, “Well, I think it's going to be a thing, just let me get through my presentation and you can decide then.” Along with that, for the next five or six years, the NIH would not touch us with a 10-foot pole. But, in 2003, the Michael J. Fox Foundation put out a request for applications on the role of inflammation in Parkinson's disease, and we got that first grant. They gave us our big break, and without them we would not be where we are today. Now it's quite well-established that the immune system and inflammation play very important and complex roles, not just in Parkinson's, but in all neurodegenerative and neurological conditions. I think it's important to recognize that it's hard to be avant-garde, but when the topic eventually catches on, you should welcome it because it means now you have made a difference. The more people working on a problem, the sooner we can understand it. You have to be able to fight and stand up for what you really think is worth investigating. We're not always right, but as long as it's a testable hypothesis, that's all that matters. Have you ever had any surprises in your career? The first big surprise was when we were developing inhibitors for TNF. There are two arms of the TNF pathway, the soluble TNF and the membrane bound TNF, and those two arms of the pathway have very different biologies. People did not really recognize that. The membrane-bound TNF is very important for the development of the immune system, fighting infection, and myelination. But when it gets cleaved to soluble form, that's the cytokine that sustains inflammatory responses. Initially, we thought it would be necessary to block both in order to be competitive with the currently FDA-approved anti-TNF inhibitors which block both forms of TNF, but in fact the better strategy is to develop treatments that target the soluble and not the membrane-bound one, so that we can have effective treatments for chronic inflammatory diseases like Crohn's disease, psoriasis, etc., without making people immunocompromised at the same time. It's always a surprise when you find that inflammation plays a very interesting role in places where you do not expect it. Also, you do not want to interfere with all inflammation—acute inflammation is critically important for fighting infection and wound healing and you do not want to immunosuppress individuals; you do not want to kill or maim microglia and certainly not astrocytes or oligodendrocytes. Finally, another weird thing is that there's a lot of data showing that the anti-inflammatories and TNF biologics that do not get into the brain still may be associated with lower risk for dementia and Parkinsonism. How does that work? It is turning out that maybe peripheral inflammation has an effect on the brain. This changes the landscape for Pharma. If compounds do not have to get into the brain to treat some of these diseases, then there's a lot of hope. We need to figure out if getting into the brain is already too late. I think we need to identify where the diseases start, maybe in the periphery for certain individuals. Perhaps the inflammatory diseases that are so endemic in our population are risk factors for these age-related diseases like dementia for individuals with comorbidities. Would you like to address anything about being an underrepresented minority? Sure. When I was growing up, I never felt like a second-class citizen or an underrepresented minority (URM). I grew up on the border in El Paso, Texas; I went to an all-girls Catholic school; I knew that I wanted to study science and biology, and my parents knew that I was going to move away and go to college somewhere. On the U.S. border, I was one of many Mexican–American U.S.-born students, and I never felt discriminated against. When I went to Stanford, it was such a rich and diverse student body that I still did not feel discriminated against. When I went to grad school, I started looking at the student body, then the faculty, and then the higher-up positions and realized that it became a pyramid—that there are fewer women and fewer people of color as you look at the layers headed towards the top. That definitely made an impression on me, and I thought: Why is that? And a lot of people would like to say, well, it's a self-imposed ceiling, women do not want to play the game, be like men, or whatever. I still do not know why that is. It may be a generational thing—my own mother had a lot of hang-ups about if you are lady-like or not, but she also raised me to never take a backseat and to always have a seat at the table. My mother and father were both born in Mexico, and they fought really hard to give us opportunities that they never had. I've realized that you have to stay in the game so you can be a role model for other people who do not think they can make it. My goal, even though I'm quite busy with science and administration, is to make time for community outreach activities, inspire other Hispanic Americans, Mexican Americans, people of color, to stay in science and to seal up the leaky pipeline. We need them to stay in the game. I've also learned that you have to ignore comments like—How did you get here? Did you get here because of some affirmative action or something? You just cannot let that inhibit you. People will have to accept your ideas and your worth. We all suffer from imposter syndrome, and people of color and women are especially good at it. It's important to show up, it's important to be a role model. You can act confidently, and then the feelings of confidence will come later. That's a famous quote from a book I really like: The confidence gap: A guide to overcoming fear and self-doubt (Harris, 2011). Many people who appear confident did not start that way, but became confident by acting confidently. I think in the vernacular of the day, it's fake it till you make it. Yes! Anything you'd like to add for EJN readers, members of FENS? I think it so important now to have an international, multidisciplinary community of scientists. We get more done and have more reach if we work together. I think it's really important to accept and celebrate the cultural differences among Europe, Asia, the Americas, Australia and to form stronger networks, certainly between women scientists, but also to get allies into our networks. We did not make it by just doing it ourselves. One framework for developing and supporting networks, particularly in STEM, that I learned about through a collaboration with my good friend and colleague Anita Corbett at Emory and that I quite like is called The Thrive Mosaic. The mosaic was developed by Robin Chapman, who is at the Harvard Kennedy School (Chapman, 2018). It is a mentoring scheme, and it's a way to divide mentoring into five or six buckets—you have associates, you have a mentor, you have coach, you have connectors. It defines a mentor–mentee relationship in a better, more deliverable, way. One person cannot do it all. She also talks about how important it is for URMs in STEM to have buy-in from people who are not URMs. One of the best ways to be successful is to have allies who are not URMs, who can serve as connectors. They can use their positions of privilege to connect, promote, and sponsor you. She advocates helping URMs in science to form stronger networks among themselves, figure out how to network more effectively, and how to be more specific about what they need when they approach someone. It's totally changed my way of thinking, including even how I ask people to help me when I need something. It's an exciting time to be a person of color—we are finally getting a lot of traction for allyship. We are learning how to better present ourselves to the world and to ask for what we need. It's an exciting time to be mentoring the next generation, those who will carry the baton. Any other books you would like to recommend? Another one that's incredible for having that tough conversation between a trainee and a mentor, to build that trust and communication, break down communication barriers between mentors and students is: Crucial conversations: Tools for talking when stakes are high (Patterson, 2012). I also read a really great leadership book when I first got to UF, recommended to our Fixel Leadership Academy by our director Michael Okun, called Give and take: A revolutionary approach to success (Grant, 2013). It's a really good treatise on giving—who is a giver, who's a taker, who's a fake giver, or a faker and how to recognize those things, so that you do not get taken advantage of and maybe still do good in the world. Thank you for your time. We really appreciate your unique and valuable insight. This series was inspired by the EJN Diversity and Inclusion Initiative, which includes past and present members of the Senior EJN Editorial Team. The goal of the initiative is to bring visibility and recognition to all scientists in our global community, particularly those from previously poorly represented groups. Dr. Tansey is a former employee of and co-inventor on the Xencor Inc. patents describing the dominant-negative TNFs and is a consultant to and has stock ownership in INmune Bio, which has licensed XPro1595 (pegipanermin) for neurological indications. This interview was edited for length and clarity by DLH and MGT. The peer review history for this article is available at https://publons.com/publon/10.1111/ejn.15578. The peer review history for this article is available at https://publons.com/publon/10.1111/ejn.15578.